ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2210+7G>T (rs374675118)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001086839 SCV000253153 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000241688 SCV000303163 likely benign not specified criteria provided, single submitter clinical testing
Color RCV000579831 SCV000685024 likely benign Hereditary cancer-predisposing syndrome 2015-12-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000197873 SCV001134352 likely benign not provided 2019-02-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000241688 SCV001339201 likely benign not specified 2020-03-25 criteria provided, single submitter clinical testing Variant summary: MSH2 c.2210+7G>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.4e-05 in 251400 control chromosomes in the gnomad database. Haraldsdottir_2017 reports the variant at a frequency of 0.00969 in the Icelandic population, which is significantly higher than the expected for a pathogenic variant in MSH2 causing Hereditary Non-Polyposis Colon Cancer (0.00057), suggesting the variant is a polymorphism in this population. c.2210+7G>T has been reported in the literature in an individual affected with Hereditary Non-Polyposis Colon Cancer, and was reported to have an odds ration less than 1, with a statistically significant p-value, suggesting the variant is not associated with increased risk of disease (Haraldsdottir_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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